Postprandial C-Peptide to Glucose Ratio as a Marker of β Cell Function: Implication for the Management of Type 2 Diabetes

Abstract

C-peptide is secreted from pancreatic β cells at an equimolar ratio to insulin. Since, in contrast to insulin, C-peptide is not extracted by the liver and other organs, C-peptide reflects endogenous insulin secretion more accurately than insulin. C-peptide is therefore used as a marker of β cell function. C-peptide has been mainly used to assess the presence of an insulin-dependent state for the diagnosis of type 1 diabetes. However, recent studies have revealed that β cell dysfunction is also a core deficit of type 2 diabetes, and residual β cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. This review summarizes the role of C-peptide, especially the postprandial C-peptide to glucose ratio which likely better reflects maximum β cell secretory capacity compared with the fasting ratio in assessing β cell function, and discusses perspectives on its clinical utility for managing glycemic control in patients with type 2 diabetes.

Keywords: C-peptide; postprandial; type 2 diabetes; β cell function.

Figure 1

Concepts of the pathogenesis of type 1 and type 2 diabetes (T1DM and T2DM). Reduction in β cell mass and insulin secretion are greater in T1DM than T2DM.

Figure 2

Comparison among C-peptide indices for predicting need for future insulin therapy (receiver operating characteristic (ROC) analysis). FCPR: fasting C-peptide; FCPRI: fasting C-peptide to glucose ratio; PCPR: postprandial C-peptide; PCPRI: postprandial C-peptide to glucose ratio; uCPR: 24 h urinary C-peptide; uCPRI: uCPR divided by fasting glucose level. Area under the curve (AUC) of PCPRI was the greatest (AUC: 0.779) among the indices, indicating the highest predictive value. Adapted from reference [8].

Figure 3

Hypothesis for change in β cell function and mass during development of abnormal glucose tolerance. The magnitude of the increased demand for insulin due to insulin resistance caused by excess caloric intake and physical inactivity exceeds the magnitude of β cell mass expansion, resulting in an increase in β cell workload. In individuals who are susceptible to T2DM, increased β cell workload may lead to β cell failure and the development of T2DM. Adopted from reference [2]. NGT: normal glucose tolerance; IGT: impaired glucose tolerance.